Non-ablative photonic devices and related methods

ABSTRACT

A method of delivering light energy to a pathological tissue includes emitting light energy from a first optical element within a cannula, producing a substantially uniform irradiance profile from the light energy within the cannula, transmitting the light energy emitted from the first optical element through a second optical element in thermal contact with a distal end of the cannula to the pathological tissue without ablating the pathological tissue, and conducting thermal energy from the pathological tissue through the second optical element and to the cannula.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. Application No.17/303,765 filed Jun. 7, 2021, which is a continuation application ofU.S. Application No. 16/111,735, filed Aug. 24, 2018, which claimspriority to U.S. Provisional Pat. Application No. 62/552,299, filed onAug. 30, 2017 and entitled “Non-ablative Photonic Devices and RelatedMethods,” the entire contents of each of these disclosure areincorporated herein by reference.

TECHNICAL FIELD

This disclosure relates to non-ablative photonic devices and relatedmethods of delivering photonic therapy to pathological tissues.

BACKGROUND

Light energy (e.g., visible light and infrared light in theelectromagnetic spectrum from about 400 nm to about 14 µm) can be usedto treat various pathological tissues on human patients or other animalbodies. In some instances, light treatments may be invasive and/orinclude focused, pulsed light energy (e.g., having high peak irradianceand high peak energy), which can ablate tissues. Ablative treatments canpotentially harm healthy tissues surrounding pathological tissues. Inother instances, light treatments may be invasive and/or include highaverage irradiances, which may potentially carbonize the tissues (i.e.,both pathological tissues and healthy tissues). It is highly desirableto precisely control light energy dosages and thermal energy generatedby tissue absorption of light energy to achieve safe and effectivetherapeutic results.

SUMMARY

In general, this disclosure relates to photonic devices (e.g., lightdelivery assemblies) for light sources (e.g., lasers) used to delivernon-focused, controlled photonic therapy to pathological tissues inmammals. Such photonic devices are advantageously designed to benon-invasive and accordingly may be used for direct access to certainareas of a body, such as skin or various body cavities. The photonicdevices are non-ablative devices, such that the devices can deliverlight energy to treat a tissue without vaporizing the tissue, explodingthe tissue, burning the tissue, carbonizing the tissue, or otherwiseremoving or eroding the tissue. Rather, the photonic devices aredesigned and constructed to radiate light energy in the visible andinfrared wavelength ranges onto a human patient or another animal bodyto destroy a pathological tissue by heating the pathological tissue. Thephotonic devices can produce uniform irradiance profiles characterizedby a substantially constant intensity, such that a pathological tissueirradiated by the light energy can be adequately, uniformly, and gentlytreated (e.g., heated). Such photonic devices include a cannula and athermally conductive element (e.g., a rod) secured to a distal end ofthe cannula. The thermally conductive element is made of a material thatcan be directly exposed to tissues and bodily fluids, can transmit lightenergy from a light source to a tissue, and can conduct heat energy fromthe tissue to the cannula. The thermally conductive element has a shape(e.g., a cylindrical shape) that is optimized according tothermodynamics of heat flow such that maximal light energy can bedelivered to a surface of a pathological tissue without ablating thetissue. Therefore, maximal light energy can be delivered at any givendepth of the pathological tissue to cause photothermal necrosis todestroy the pathological tissue.

Advantageously, the photonic devices can also deliver light energy tonanoparticles or other particles within pathological regions (e.g.,tumors or other pathological tissues) to provide photonic therapy. Forexample, nanoparticles are designed to preferentially accumulate withina pathological tissue and to selectively absorb a wavelength to be usedfor photonic therapy delivered to the pathological tissue. Thenanoparticles can be selectively heated by the light energy and canadvantageously destroy the pathological tissue without harmingsurrounding healthy tissues. In some embodiments, the photonic devicescan deliver photonic therapy directly to a pathological tissue (e.g.,without the presence of nanoparticles).

In one aspect, a non-ablative photonic device includes a cannula, afirst optical element located adjacent a proximal end of the cannula andconfigured to produce light energy with a substantially uniformirradiance profile, and a second optical element in thermal contact witha distal end of the cannula. The second optical element is configured totransmit the light energy emitted from the first optical element to apathological tissue located distal to the second optical element andconfigured to conduct thermal energy from the pathological tissue to thecannula.

Embodiments may include one or more of the following features.

In some embodiments, the first optical element is an optical fiber.

In certain embodiments, the second optical element is a waveguide.

In some embodiments, the second optical element is a cylindricalsapphire rod.

In certain embodiments, the non-ablative photonic device includes alaser that generates the light energy.

In some embodiments, the non-ablative photonic device includes alight-emitting diode (LED) that generates the light energy.

In certain embodiments, the substantially uniform irradiance profile hasa non-circular cross-sectional shape.

In some embodiments, the substantially uniform irradiance profile has ahexagonal cross-sectional shape or a square cross-sectional shape.

In certain embodiments, the substantially uniform irradiance profile istransmitted to a distal surface of the second optical element.

In some embodiments, the first optical element terminates near theproximal end of the cannula.

In certain embodiments, the non-ablative photonic device furtherincludes one or more lenses positioned within the cannula between thefirst optical element and the second optical element and configured todirect the laser beam away from an internal surface of the cannula tolimit reflection losses within the cannula.

In some embodiments, the first optical element extends distally into alumen of the cannula.

In another aspect, a light delivery assembly includes multiplenon-ablative photonic devices.

In another aspect, a method of delivering light energy to a pathologicaltissue includes emitting light energy from a first optical elementwithin a cannula, producing a substantially uniform irradiance profilefrom the light energy within the cannula, transmitting the light energyemitted from the first optical element through a second optical elementin thermal contact with a distal end of the cannula to the pathologicaltissue without ablating the pathological tissue, and conducting thermalenergy from the pathological tissue through the second optical elementand to the cannula.

Embodiments may include one or more of the following features.

In some embodiments, the first optical element is an optical fiber.

In certain embodiments, the second optical element is a waveguide.

In some embodiments, the second optical element is a cylindricalsapphire rod.

In certain embodiments, the method further includes generating the lightenergy with a laser.

In some embodiments, the method further includes generating the lightenergy with a light-emitting diode (LED).

In some embodiments, the substantially uniform irradiance profile has anon-circular cross-sectional shape.

In certain embodiments, the substantially uniform irradiance profile hasa hexagonal cross-sectional shape or a square cross-sectional shape.

In some embodiments, the method further includes transmitting thesubstantially uniform irradiance profile to a distal surface of thesecond optical element.

In certain embodiments, the method further includes directing the lightenergy away from an internal surface of the cannula through one or morelenses positioned within the cannula between the first optical elementand the second optical element to limit reflection losses within thecannula.

In some embodiments, the method further includes transmitting the lightenergy through the second optical element to nanoparticles bound to thepathological tissue.

In some embodiments, the method further includes emitting light energyfrom a third optical element within a second cannula disposed adjacentthe first cannula, producing a second substantially uniform irradianceprofile from the light energy within the second cannula, transmittingthe light energy emitted from the third optical element through a fourthoptical element in thermal contact with a distal end of the secondcannula to the pathological tissue to overlap the first and secondsubstantially uniform irradiance profiles beneath a surface of thepathological tissue without ablating the pathological tissue, andconducting thermal energy from the pathological tissue through thefourth optical element and to the second cannula.

Other aspects, features, and advantages will be apparent from thedescription, the drawings, and the claims.

DESCRIPTION OF DRAWINGS

This patent or patent application publication contains at least onedrawing executed in color. Copies of this patent or patent applicationpublication with color drawing(s) will be provided by the USPTO uponrequest and payment of an associated fee.

FIG. 1 is a longitudinal cross-sectional view of a photonic device.

FIG. 2 is a perspective view of a cannula and a transmissive element ofthe photonic device of FIG. 1 .

FIG. 3 is an end view of the photonic device of FIG. 1 , showing acentered light source.

FIG. 4 is an end view of a photonic device, showing an off-center lightsource.

FIG. 5 is a set of images of a distal surface of a transmissive elementof the photonic device of FIG. 4 , acquired at varying distances fromthe distal surface.

FIG. 6 is a cross-sectional view of a portion of a photonic device thatincludes imaging lenses housed within a cannula.

FIG. 7 is a perspective view of a portion of the cannula of the photonicdevice of FIG. 6 .

FIG. 8 is a partial schematic of a sequential ray trace of a light beamtransmitted through optical elements of a photonic device including alens assembly.

FIG. 9 is a full schematic of the sequential ray trace of FIG. 8 ,inclusive of a path along a fiber optic cable assembly.

FIG. 10 is an image associated with a ray trace and optical designconfiguration of FIGS. 8 and 9 , exemplifying proper design and adequatealignment (e.g., a near central alignment) using a hexagonal core fiber,and delivering a uniform irradiance at a distal surface of a conductiveelement positioned along a distal end region of a cannula.

FIG. 11 is an image of a distal surface of a conductive elementpositioned along a distal end region of a cannula and a light irradianceprofile positioned a few millimeters from the distal surface.

FIG. 12 is an expanded view of the light irradiance profile of FIG. 11 ,omitting the cannula.

FIG. 13 is a beam intensity profile of the irradiance distribution ofthe beam exiting the cannula and corresponding to the image shown inFIG. 10 .

FIG. 14 is a beam intensity profile showing sub-optimal, non-uniformirradiance that is potentially inadequate for photonic therapy.

FIG. 15 is a beam intensity profile showing sub-optimal, non-uniformirradiance that is potentially inadequate for photonic therapy.

FIG. 16 is a flowchart illustrating a method of using photonic devicesdescribed herein.

FIG. 17 is a cross-sectional view of multiple photonic devices arrangedadjacent one another to deliver overlapping light beams at a depth belowa surface of a pathological tissue.

DETAILED DESCRIPTION

FIG. 1 illustrates a cross-sectional view of an example photonic device100 designed to deliver photonic therapy (e.g., electromagneticradiation or light energy) to a pathological tissue on a human oranother animal (e.g., a dog or a cat). Example pathological tissuesinclude tumors (e.g., melanomas), lesions, ulcers, bacterial infectedtissues (e.g., methicillin-resistant staphylococcus aureus (MRSA)), andother pathological regions. The photonic device 100 is a non-ablativelight delivery assembly that is constructed to deliver photonic therapyto particles (e.g., nanoparticles) adjacent (e.g., bound to, positionedon, or positioned within) the pathological tissue and to deliverphotonic therapy directly to the pathological tissue, depending onvarious parameters, such as a wavelength of the light energy, anirradiance at the skin or other external tissue, a surface temperatureat the skin or other external tissue, and a treatment or exposure time.

In the depicted embodiment, the photonic device 100 includes a cannula102 and a fiber optic cable assembly 104. The fiber optic cable assembly104 includes a ridged outer tubular housing 118, an optical fiber 108protruding from the tubular housing 118 and extending distally into thecannula 102, and a male connector 106 joining a distal end of thetubular housing 118 with a female connector 120 that forms a proximalend of the cannula 102. The photonic device 100 further includes a fibersupport member 110 disposed about the optical fiber 108 within thecannula 102 and an optically transparent, thermally conductive element114 (e.g., a transmissive rod element that serves as a waveguide) thatis secured in thermal contact with a distal end region 116 of thecannula 102.

A distance between an output end 130 (e.g., a distal end) of the opticalfiber 108 and a proximal surface 128 of the transmissive element 114 canbe adjusted. The tubular housing 118 protects the optical fiber 108 andallows the optical fiber 108 to bend for flexible manipulation of thecannula 102. In some embodiments, the tubular housing 118 and theoptical fiber 108 therein have a bend radius in a range of about 10 mmto about 100 mm. The tubular housing 118 and the male connector 106typically have an assembled length of about 1 m to about 5 m (e.g.,about 3 m). The tubular housing 118 typically has an internal diameterof about 1 mm to about 10 mm (e.g., about 3 mm) and typically has anouter diameter of less than about 10 mm. The tubular housing 118 istypically made of one or more materials, including stainless steel. Themale connector and the female connector 120 may be SubMiniature versionA (SMA) connectors or other types of connectors (e.g., ST connectors)suitable to the application.

Referring to FIGS. 1 and 2 , the cannula 102 allows passage of lightemitted from the output end 130 of the optical fiber 108 through theoptically transparent, transmissive element 114 to a surface of thepathological tissue for photonic treatment. The cannula 102 has a mainportion 122 (e.g., a central portion between the female connector 120and the distal end region 116) that surrounds the output end 130 of theoptical fiber 108. The cannula 102 also defines four holes 124 along thedistal end region 116 that provide reservoirs for a thermally conductiveadhesive substance that may be used to attach the transmissive element114 to the cannula 102, as will be discussed in more detail below. Theholes 124 typically have a diameter of about 0.5 mm to about 3.0 mm(e.g., about 1.0 mm). The cannula 102 is typically made of one or morematerials that can efficiently reflect and scatter light, minimizereflection losses (e.g., and associated energy losses) of a light beam,and dissipate heat transferred from the surface of the pathologicaltissue through the transmissive element 114. Such example materialsinclude stainless steel and oxygen free copper.

A length of the cannula 102 that is sufficient for housing the opticalfiber 108 also provides manipulability of the photonic device 100 (e.g.,improves an ease of using the photonic device 100), increases aheatsinking surface of the cannula 102, minimizes or prevents internalreflection losses, and avoids the need for special coatings that wouldotherwise be needed to achieve efficient coupling of light energyemitted from the optical fiber 108 to the pathological tissue. Aselected length, internal diameter, and wall thickness of the mainportion 122 of the cannula 102 can vary, depending on an area and/or avolume of a pathological tissue to be treated. In the depicted exampleembodiment of the photonic device 100 (e.g., which may be used forphotonic ablation of cancerous tumors less than 2-3 cm in diameter and1-2 cm deep), the main portion 122 has a length of about 120 mm, aninternal diameter of about 7 mm, and a wall thickness of about 2 mm. Thecannula 102 may take on a variety of dimensions and proportions so longas the cannula 102 is long enough to house a length of the transmissiveelement 114, is practically sized for handling, and is suitably sized toachieve adequate thermal management. In some embodiments, an internalsurface of the cannula 102 may be characterized by control roughening tohomogenize a distribution of the light intensity at a distal surface 126of the transmissive element 114.

The transmissive element 114 is made of one or more materials thattransmit light wavelengths in a range of about 400 nm to about 14 µm(e.g., including visible light energy and near infrared (NIR) lightenergy), that serve as adequate heat conductors, and that sink excessiveheat to prevent the emitted light energy from burning the pathologicaltissue. Example materials from which the transmissive element 114 may bemade include sapphire, diamond, calcium fluoride, and chalcogenideglasses. For example, sapphire may efficiently transmit lightwavelengths in the NIR range, up to about 12 µm. The transmissiveelement 114 transmits the light energy emitted from the optical fiber108 through the distal end region 116 of the cannula 102 to deliver thelight energy to the pathological tissue. The transmissive element 114also transmits heat energy generated at the pathological tissue to thecooler material of the cannula 102 according to thermal gradientscreated by contact between the transmissive element 114 and the cannula102. Such thermal gradients generally depend on parameters including astructural form of the transmissive element 114, material properties ofthe transmissive element 114, and an arrangement of the transmissiveelement 114 with respect to the cannula 102. Heat energy is safelyradiated or conducted from the cannula 102 to other thermally conductivesurfaces (e.g., the metal jacket of the optical fiber 108).

In some embodiments, the transmissive element 114 is coated (e.g.,brazed) with a metalized substance (e.g., silver, gold, or oxygen freecopper) to maximize thermal contact between the transmissive element 114and the cannula 102. In some embodiments, the transmissive element 114is not coated with such a metalized substance. For example, thetransmissive element 114 may be adhered to an inner surface of thecannula 102 with a thermally conductive adhesive substance (e.g., anepoxy substance). In some embodiments, the transmissive element 114 canbe attached to the inner surface of the cannula 102 without an adhesivesubstance, but with a press fit, to improve surface contact between thetransmissive element 114 and the cannula 102 and thereby improve heatdissipation.

The transmissive element 114 is a cylindrical structure with an aspectratio of less than one for optimal heat transfer from a distal surface126 of the transmissive element 114 to the cannula 102. For example, thetransmissive element 114 typically has a length of about 45 mm to about55 mm (e.g., about 50 mm) and a diameter of about 5.9 mm to about 6.1 mm(e.g., about 6.0 mm). In some embodiments, the transmissive element 114has a fine, uniform diffuser polish along the distal surface 126 and a40/60 scratch and dig quality along the proximal surface 128. Thediffuser polish can improve the uniformity of the light intensitydistribution through the transmissive element 114, thereby eliminatinghot spots and making heat deposition and distribution at the surface ofthe pathological tissue (i.e., which in contact with the distal surface126 of the transmissive element 114) more uniform. The scratch and digfinish can eliminate or significantly minimize large pits or scratchesin the proximal surface 128 that would otherwise affect both theefficiency of light transmission from the optical fiber 108 to thepathological tissue, as well as the light intensity distribution at thesurface of the pathological tissue, which would ideally have a perfectlyuniform intensity. In some embodiments, the uniform diffuser polish andthe scratch and dig finish may be located on opposite sides of thetransmissive element 114. In some embodiments, the transmissive element114 may not include either or both of the diffuser polish and thescratch and dig surface finishes.

In some embodiments, either or both of the distal and proximal surfaces126, 128 of the transmissive element 114 may be coated with ananti-reflection (AR) coating at an appropriate light wavelength tominimize reflections of the laser light emitted from the optical fiber108. In some embodiments, the distal surface 126 of the transmissiveelement 114 may be coated with materials (e.g., diamond) that bothimprove thermal contact with the pathological tissue and improve thermaltransmission from the pathological region to the transmissive element114 with minimal or no impact to the transmission of light energythrough the transmissive element 114. Additionally, in some embodiments,the transmissive element 114 extends past the distal end region 116 ofthe cannula 102 by about 1.0 mm to about 3.0 mm (e.g., about 2.0 mm) tolimit between the cannula 108 and the pathological tissue.

Still referring to FIGS. 1 and 2 , the optical fiber 108 is coupled to alight source (not shown), transmits light energy emitted from the lightsource, and emits the light energy towards the transmissive element 114.The optical fiber 108 is typically made of one or more materials,including fused quartz and fused silica. In some embodiments, the lightsource is a laser. In such embodiments, the optical fiber 108 may have anumerical aperture (NA) of 0.22 and be designed to produce a uniformintensity beam profile. For example, the optical fiber 108 may produceuniform intensity beams profiles with a circular cross-sectional shape,a hexagonal cross-sectional shape, a square cross-sectional shape, orany other suitable uniform intensity shape. During operation of thephotonic device 100, a temperature of the pathological tissue beingtreated increases as a function of time that the light source isactivated, while the thermally conductive surfaces of the cannula 102,the tube 104, and the male connector 106 dissipate heat transmitted fromthe surface of the pathological tissue through the transmissive element114. Therefore, the temperature at the surface of the pathologicaltissue remains substantially constant over time.

The optical fiber 108 extends distally into the main portion 122 of thecannula 102 such that a beam area of the emitted light is about 60% toabout 80% of an area of the distal surface 126 of the transmissiveelement 114. For example, the output end 130 of the optical fiber 108 istypically spaced from the proximal surface 128 of the transmissiveelement 114 by a distance of about 0.1 cm to about 1.0 cm. In an exampleembodiment where the optical fiber 108 has a 0.22 NA and a clearaperture of 8 mm, the output end 130 of the optical fiber 108 may bespaced about 3 mm from the proximal surface 128 of the transmissiveelement 114. The fiber support member 110 defines a central longitudinalopening 132 that supports and centers the optical fiber 108 within thecannula 102. The fiber support member 110 may be attached to an internalsurface of the cannula 102 with an adhesive substance (e.g., an epoxysubstance). Example materials from which the fiber support member 110and may be made include as polylactic acid (PLA), stainless steel, andpolytetrafluoroethylene (PTFE). The fiber support member 110 may beembodied as a grommet, a washer, a hollow cylinder, or another similarstructure.

FIGS. 3 and 4 respectively illustrate end views of the photonic device100 (e.g., including the fiber support member 110 adhered to the cannula102) and another photonic device 180 (e.g., a visible laser) that issimilar in construction and function to the photonic device 100, exceptthat the photonic device 180 does not include the fiber support member110. Accordingly, the photonic device 180 includes the other componentsof the photonic device 100. The decentering effects of omitting thefiber support member 110 can be clearly seen in FIG. 4 . For example,despite a stiffness of the optical fiber 108, the optical fiber 108extends into the cannula 102 at an off-axis (e.g., off-center)orientation (e.g., up to about 3 mm away from an axis of the cannula102) without centering provided by the fiber support member 110.Detectors placed at the distal surface 126 of the transmissive element114, at a first distance of about 10 mm from the distal surface 126, andat a second distance of about 20 mm from the distal surface 126 producethe images shown in FIG. 5 , which illustrate the off-axis position ofthe output end 130 of the optical fiber 108 within the cannula 102 ofthe photonic device 180.

Other embodiments of photonic devices that are similar to the photonicdevice 100 in construction and/or function are possible. For example,while the photonic device 100 has been described and illustrated ashaving a configuration in which the optical fiber 108 extends distallyinto the cannula 102, in some embodiments, a photonic device that issimilar in function to the photonic device 100 may include one or moredifferent features or configurations, such as imaging lenses that relaylight energy to a distal surface of a sapphire rod (e.g., therebycompletely eliminating internal reflection losses in a cannula) or suchas lacking the optical fiber 108 altogether in lieu of a light source(e.g., a light-emitting diode (LED)) inside of a cannula at anappropriate distance from a sapphire rod.

For example, FIG. 6 illustrates an internal side view of a portion of aphotonic device 200 (e.g., a non-ablative laser) that includes a lensassembly 240 for imaging (e.g., relaying) light energy from an outputend (e.g., a distal end) of an optical fiber (not shown) to a surface ofa pathological tissue (e.g., located at the distal surface 126 of thetransmissive element 114) without incurring reflection losses at asurface of a cannula 202. Like the photonic device 100, the photonicdevice 200 is designed to deliver photonic therapy to a pathologicaltissue in a mammal. That is, the photonic device 200 can deliverphotonic therapy to particles bound to the pathological tissue ordeliver photonic therapy directly to the pathological tissue. Thephotonic device 200 includes the cannula 202 and the transmissiveelement 114 of the photonic device 100. The photonic device 200 alsoincludes a fiber optic cable assembly (not shown) that is similar to thefiber optic cable assembly 104 of the photonic device 100, including thetubular housing 118, the optical fiber 108, and the male connector 106,except that the optical fiber 108 does not extend as far distally pastthe male connector 106 as compared to the fiber optical cable assembly104. Such a configuration permits the optical fiber 108 to be insertedand terminate within a female connector 220 that forms a proximal end ofthe cannula 202 (e.g., as opposed to extending distally within a mainportion 222 of the cannula 202). FIG. 7 illustrates a perspective viewof a portion of the cannula 202. The cannula 202 is substantiallysimilar in construction and function to the cannula 102 of the photonicdevice 100, except that the cannula 202 includes a port 260 thatfacilitates assembly of the lens assembly 240 with the cannula 202, aswill be discussed in more detail below.

Referring again to FIG. 6 , in the depicted embodiment, the lensassembly 240 includes a cylindrical support base 242, a proximal lens244, a distal lens 246, and a spacer 248 that secures the lenses 244,246 at fixed positions within the cannula 202. For example, the lenses244, 246 may be bonded to an inner surface of the spacer 248 with asuitable bonding agent, such as a suitable epoxy adhesive. Thecylindrical support base 242 delivers the light energy emitted from theoptical fiber 108 to the proximal lens 244 and defines a distancebetween the output end 130 of the optical fiber 108 and the proximallens 244. The cylindrical support base 242 may have a length of about 20mm to about 400 mm (e.g., about 120 mm) and may be made of one or morematerials including stainless steel, oxygen free copper, aluminum, andother materials.

The output end 130 of the optical fiber 108 (not shown) is fixed inposition relative to the lens 242 by the SMA connector design providedby the male connector 106 (not shown) and the female connector 220. Inthe example embodiment of the photonic device 200, the transmissiveelement 114 does not include the fine diffuser polish and the 40/60scratch and dig quality of the end surfaces 126, 128 to achieve auniform light intensity profile. Instead, the lens assembly 240 isdesigned to relay the uniform light intensity profile generated by thefiber coupled light source to the distal surface 126 of the transmissiveelement 114. Design parameters (e.g., lens focal lengths, separationbetween lenses, etc.) of the lens assembly 240 can be used to tailor ashape of the light beam and/or an intensity distribution at the surfaceof the pathological tissue as needed to maximize the effectiveness ofthe photonic therapy (e.g., to produce a square beam shape with asignificantly uniform intensity distribution).

The lenses 244, 246 have focal lengths and positions along the cannula202 that are appropriate for imaging the distal end of the optical fiberonto the distal surface 126 of the transmissive element 114. The lenses244, 246 typically include an anti-reflective (AR) coating to minimizereflection losses. The spacer 248 may be made of a resin or one or moreother materials. The spacer 248 may be fixed in position with respect tothe cannula 202 by a fastener (e.g., a set screw) disposed within theport 260 of the cannula 202.

Inclusion of the lenses 244, 246 within the photonic device 200facilitates tuning of both a size and a shape of the light beam profileat a surface of a pathological tissue such that a uniform intensitydistribution is delivered to the pathological tissue. For example,inclusion of the lenses 244, 246 increases a transmission efficiency oflight energy exiting the optical fiber and relayed to a pathologicalsurface as compared to similar devices without such lenses. The lenses244, 246 also allow the emitted laser beam to penetrate the pathologicaltissue to reach a depth (e.g., up to about 2 cm) greater than a depth(e.g., up to about 6 mm) that can be treated with conventional deviceswithout burning a surface of the pathological tissue at which thephotonic device 200 is directed by imaging the optical fiber onto thepathological tissue. Because a uniform thermal distribution is produced,more power can be applied without burning the pathological tissue suchthat adequate photonic energy can be delivered to the pathologicaltissue at greater depths. In this manner, the photonic device 200 candeliver photonic therapy to the pathological tissue to destroy thepathological tissue from the bottom up without burning the surface,thereby influencing a thermal gradient within the pathological region.In some implementations, power in a range of about 1 W to about 15 W maybe input to the photonic device 200.

FIGS. 8 and 9 respectively illustrate a partial schematic (e.g.,excluding a path along a fiber optic cable assembly) and a fullschematic (e.g., including the path along the fiber optic cableassembly) of an example optical design and example ray traces 250. Theray traces 250 show a light source transmitted through a photonic device300 that is substantially similar in construction and function to thephotonic device 200 of FIG. 5 , except that the photonic device 300includes an optical fiber that produces a uniform hexagonal lightintensity distribution profile. For example, the photonic device 300includes several components of the photonic device 200 (e.g., thecannula 202, the lens assembly 240, and the transmissive element 114),some of which are not shown in FIGS. 8 and 9 . The optical fiber of thephotonic device 300 has a 0.22 NA and a cross-sectional width (e.g., acore diameter) of about 600 µm. The lens assembly 240 (lenses 244, 246shown in FIGS. 8 and 9 ) images the intensity profile distribution atthe distal end of the optical fiber (i.e., located adjacent the proximallens 244) onto the distal surface 126 of the transmissive element 114.Images may be acquired of the distal surface 126 of the transmissiveelement 114 at various distances from the transmissive element 114, asindicated by positions 252, 254 in FIG. 9 .

FIG. 10 illustrates an image 262 of the cross-sectional shape of thehexagonal uniform intensity distribution generated on the distal surface126 of the transmissive element 114 of the photonic device 300 describedwith respect to FIGS. 8 and 9 . FIGS. 11 and 12 illustrate images 264,266 of the light intensity distribution generated on a plane spacedapart from the distal surface 126 of the transmissive element 114 ofdifferent photonic devices producing square and circular cross-sectionalshapes, respectively. Such photonic devices are substantially similar inconstruction and function to the photonic device 300, except that thedevices respectively include optical fibers with square and circularcross-sectional shapes associated with the images 264, 266. Off-centerpositions of the images 262, 264, 266 can result from slack (e.g., losetolerances) between the cannula 202 and the spacer 248.

FIG. 13 illustrates a measured intensity distribution of a light profile268 resulting from the photonic device 300 employing a hexagonalcross-sectional shape generating optical fiber and properly designedimaging optics (e.g., the lenses 244, 246). In contrast to the uniformintensity distribution 268, and as shown in FIG. 14 , a conventionaloptical fiber (i.e., absent any light intensity homogenization) orinadequately diffused or homogenized light from any optical fiberproduces a non-uniform intensity profile, such as a non-uniformintensity profile 270, that peaks along a center of the laser beam anddecreases with a distance from the center of the laser beam. In otherexamples, such a conventional optical fiber may produce a non-uniformintensity profile, such as a non-uniform intensity profile 272 shown inFIG. 15 , that exhibits high intensity regions. The high intensitycentral area of Gaussian intensity profiles or the high peak irradianceareas of inadequately diffused light beams can easily have localintensity (e.g., peak irradiances that are many times that of theaverage intensity of the light beam, defined as a total power of thelight beam divided by a beam area), which can result in non-uniformwarming of the pathological tissue.

In contrast, uniform intensity light distributions have substantiallyequal peak and average irradiances characterized by a substantiallyconstant intensity, such that a pathological tissue irradiated by thelight can be uniformly treated. The substantially constant irradiance ofthe light profile 268 results in a gentle, uniform warming of thepathological tissue. In this manner, carbonization of the pathologicaltissue by high intensity peak irradiance areas can be avoided, whereasconventional devices are intentionally designed to carbonize tissue. Inthis manner, an entire surface area illuminated by the photonic device300 can be adequately treated with an optimized therapy.

The photonic devices 100, 200, 300 are non-invasive devices that candeliver photonic therapy to accessible pathological tissues. Suchaccessible pathological tissues may be located on skin or within a bodycavity (e.g., such as oral and vaginal cavities). Example pathologicaltissues include melanomas and mast cell carcinomas in humans and dogs,fibrosarcomas in cats, and, in general, non-invasively or minimallyinvisibly accessible pathological tissues of the type that could betreated cryogenically or through surgical excisions. In operation of thephotonic devices 100, 200, 300, a pathological tissue can be treated(e.g., systemically via an intravenous injection, or locally at a tumoror its main blood supply) with a dosage of nanoparticles such that thenanoparticles accumulate on and/or within the pathological tissue at adesired concentration, and do so preferentially in cancerous tissues asthese are highly vascularized. After a predetermined wait period ofabout 12 hours to about 36 hours to allow for the diffusion ofnanoparticles into the pathological tissue, the photonic devices 100,200, 300 can be positioned in contact with the surface of thepathological tissue and controlled (e.g., monitoring a surfacetemperature of the pathological tissue) to deliver 808 nm laser energywith a continuously delivered dosage of about 2 W/cm2 to about 20 W/cm²for a duration of about 5 min to the pathologic site. Delivery of thelaser dosage causes the nanoparticles to heat to a temperature in arange of about 45° C. to about 55° C., where such heating preferentiallydestroys the pathological tissue without harming surrounding healthytissues.

FIG. 16 illustrates an example process 400 for delivering photonictherapy to a pathological region. In some implementations, the methodincludes emitting light energy from a first optical element within acannula (402). In some implementations, the method further includesproducing a substantially uniform irradiance profile from the lightenergy within the cannula (404). In some implementations, the methodfurther includes transmitting the light energy emitted from the firstoptical element through a second optical element in thermal contact witha distal end of the cannula to the pathological tissue without ablatingthe pathological tissue (406). In some implementations, the methodfurther includes conducting thermal energy from the pathological tissuethrough the second optical element and to the cannula (408).

A number of embodiments have been described. Nevertheless, it will beunderstood that various modifications may be made without departing fromthe spirit and scope of the disclosure. For example, while the photonicdevices 100, 200, 300 have been described and illustrated as includingthe transmissive element 114, in some embodiments, a photonic devicethat is similar in function to either of the photonic devices 100, 200,300 may not include a rod, but use an actively cooled window. In someimplementations, such a photonic device may be more efficient (e.g., mayemit a relatively high portion of electromagnetic energy input to thecannula assembly).

While components of the photonic devices 100, 200, 300 have beendescribed and illustrated as including certain dimensions, shapes, andmaterial formulations, in some embodiments, a photonic device that issimilar in construction and function to either of the photonic devices100, 200, 300 may include one or more components that have differentdimension, shapes, and/or material formulations.

In some implementations, any of the photonic devices 100, 200, 300 maybe used in conjunction with other forms of electromagnetic energy. Forexample, concurrent application to the pathological tissue of thephotonic energy and electromagnetic fields generated by direct oralternating current, direct or pulsed electric currents, or radiofrequency would reduce the photonic energy needed to produce the desiredtherapeutic effect on the pathological tissue. Thus, such combinationswould either enhance the depths at which the photonic energy wouldproduce the desired effect and/or reduce the intensity of the photonicenergy needed at the surface of the pathological tissue.

In some implementations, using any of the photonic devices 100, 200, 300in conjunction with properly selected materials that optimize energytransfer between the transmissive element 114 and the surface of thepathological tissue (e.g., water, ultrasound gel, etc.) can produce amore intimate contact between the surface and minimize losses of thephotonic energy due to index of refraction mismatches between a materialof the transmissive element 114 and the pathological tissue.Additionally, by eliminating air gaps between the transmissive element114 and the pathological tissue, such materials can act to moreefficiently couple heat from the pathological tissue to the transmissiveelement 114 for radiative and/or conductive dissipation by the cannula.In some embodiments, the materials may additionally be infused with ananalgesic agent (e.g., lidocaine) to minimize patient discomfort.

In some implementations, using any of the photonic devices 100, 200, 300in conjunction with a cooling source (e.g., a cold air blower,thermos-electrically actively cooled cannula surface, etc.) may maximizethe photonic energy that can be delivered to the pathological tissuewithout tissue carbonization.

In some implementations, the photonic devices 100, 200, 300 may be usedto deliver photonic therapy directly to a pathological tissue (e.g.,without nanoparticles). In some implementations, a single photonicdevice 100, 200, 300 may be operated sequentially at different locationsalong the pathological tissue until a complete area of the pathologicaltissue is treated.

In other instances, multiple photonic devices 100, 200, 300 may bepositioned adjacent one another and operated in parallel (e.g., at thesame time) to treat a large region of a pathological tissue. Forexample, FIG. 17 illustrates multiple photonic devices 500 (e.g.,embodied as any of the photonic devices 100, 200, 300) arranged adjacentone another to deliver multiple light beams 501 to a pathologicaltissue. The photonic devices 500 receive input light and format theinput light with one or more optical elements 580 (e.g., embodied as theoptical fiber 108 or the lenses 244, 246). Although the light beams 501do not overlap at distal surfaces of the transmissive elements 514(e.g., at output ends of the cannulas 502), the light beams 501 dooverlap at a depth below a surface 503 of the tissue. Such overlap willproduce greater heating at a target area below the surface 503 of thetissue than could a single photonic device alone. Accordingly, in someembodiments, distal features of the cannula 502 may be sharp such that adistal end of the photonic device 500 can be inserted into a tissue toproduce any desired thermal profile at any depth of the tissue.

In some embodiments, the cannula of any of the photonic devices 100,200, 300 or of a photonic device that is similar in construction andfunction to any of the photonic devices 100, 200, 300 may be activelycooled to increase irradiance at a pathological tissue without beinglimited by thermal characteristics of the transmissive element or theambient environment such that the maximum heat that the cannula candissipate can be controlled. For example, the cannula may be activelycooled using one or more of chilled water, thermos electric coolingtechnology, heat pipes, and phase change materials.

1. (canceled)
 2. A non-ablative photonic device, comprising: a firstoptical path comprising: a first optical element configured to producefirst light energy with a substantially uniform first irradianceprofile; and a second optical element configured to transmit the firstlight energy from the first optical element to a pathological tissuelocated distal to the second optical element and configured to conductthermal energy from the pathological tissue; and a second optical pathadjacent to the first optical path, the second optical path comprising:a third optical element configured to produce second light energy with asubstantially uniform second irradiance profile; and a fourth opticalelement configured to transmit the second light energy from the thirdoptical element to the pathological tissue located distal to the fourthoptical element and configured to conduct thermal energy from thepathological tissue.
 3. The device of claim 2, wherein the first lightenergy and the second light energy do not overlap one another at atissue surface and do overlap one another at a depth below the tissuesurface.
 4. The device of claim 2, wherein the first optical elementand/or the third optical element comprises an optical fiber.
 5. Thedevice of claim 2, wherein the second optical element and/or the fourthoptical element comprises a waveguide or a cylindrical sapphire rod. 6.The device of claim 2, further comprising at least one laser thatgenerates the first light energy and/or the second light energy.
 7. Thedevice of claim 2, further comprising at least one light-emitting diode(LED) that generates the first light energy and/or the second lightenergy.
 8. The device of claim 2, wherein the first irradiance profileand/or the second irradiance profile has a non-circular cross-sectionalshape.
 9. The device of claim 2, wherein the first irradiance profileand/or the second irradiance profile has a hexagonal cross-sectionalshape or a square cross-sectional shape.
 10. The device of claim 2,wherein the first irradiance profile is transmitted to a distal surfaceof the second optical element and/or the second irradiance profile istransmitted to a distal surface of the fourth optical element.
 11. Thedevice of claim 2, further comprising one or more lenses between thefirst optical element and the second optical element.
 12. The device ofclaim 11, further comprising one or more lenses positioned between thethird optical element and the fourth optical element.
 13. A method ofdelivering light energy to a pathological tissue, the method comprising:emitting first light energy from a first optical element; producing asubstantially uniform first irradiance profile from the first lightenergy; transmitting the first light energy along a first optical pathfrom the first optical element through a distal end surface of a secondoptical element directly to a surface of the pathological tissue in anon-invasive manner without ablating the pathological tissue; conductingthermal energy away from the surface of the pathological tissue throughthe distal end surface of the second optical element; emitting secondlight energy from a third optical element; producing a substantiallyuniform second irradiance profile from the second light energy;transmitting the second light energy along a second optical path fromthe third optical element through a distal end surface of a fourthoptical element directly to the surface of the pathological tissue in anon-invasive manner without ablating the pathological tissue, the secondoptical path adjacent to the first optical path; and conducting thermalenergy away from the surface of the pathological tissue through thedistal end surface of the fourth optical element.
 14. The method ofclaim 13, wherein the first light energy and the second light energy donot overlap one another at the surface of the pathological tissue and dooverlap one another at a depth below the surface of the pathologicaltissue.
 15. The method of claim 13, wherein the first optical elementand/or the third optical element comprises an optical fiber and thesecond optical element and/or the fourth optical element is in direct,non-invasive contact with the surface of the pathological tissue. 16.The method of claim 13, wherein the second optical element and/or thefourth optical element comprises a cylindrical sapphire rod.
 17. Themethod of claim 13, further comprising generating the first light energyand/or the second light energy with a laser.
 18. The method of claim 13,further comprising generating the first light energy and/or the secondlight energy with a light-emitting diode (LED).
 19. The method of claim13, wherein the first irradiance profile and/or the second irradianceprofile has a non-circular cross-sectional shape.
 20. The method ofclaim 13, wherein the first irradiance profile and/or the secondirradiance profile has a hexagonal cross-sectional shape or a squarecross-sectional shape.
 21. The method of claim 13, further comprisingdirecting the first light energy through one or more lenses positionedbetween the first optical element and the second optical element. 22.The method of claim 21, further comprising directing the second lightenergy through one or more lenses positioned between the third opticalelement and the fourth optical element.
 23. The method of claim 13,further comprising: delivering nanoparticles to the pathological tissuesuch that the nanoparticles accumulate at the pathological tissue;transmitting the first light energy and the second light energy to thenanoparticles at the pathological tissue; and heating the nanoparticleswith the first light energy and the second light energy to destroy thepathological tissue without harming healthy tissue adjacent to thepathological tissue.